Neurodegenerative diseases (NDs) encompass an array of distinct illnesses with unique clinical manifestations, management strategies, and disease courses. Three specific diseases have been chosen for this chapter in an effort to demonstrate the diverse range of both disease characteristics and patient and family experiences with ND: amytrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and multiple sclerosis (MS). For each disease, unique aspects of care are highlighted and principles of symptom control and palliative care are outlined and reviewed.
Key clinical and epidemiologic characteristics of ALS, PD, and MS are summarized in Table 30-1 . The presentation for ALS is most often a progressive loss in motor function; of these three diseases ALS has by far the lowest incidence, despite a tremendous volume of literature addressing the associated complex care needs. Particularly for individuals older than age 80, PD is a relatively common disease in which the loss of dopaminergic neurons in the brain clinically manifests with both motor and nonmotor impairments. Multiple sclerosis most commonly presents in young adults and is an autoimmune inflammatory disease characterized by multifocal plaques of demyelination throughout the central nervous system.
| Amyotrophic Lateral Sclerosis (ALS) | Parkinson’s Disease (PD) | Multiple Sclerosis (MS) | |
|---|---|---|---|
| Prevalence | 6/100,000 | 160/100,000 | 30–80/100,000 |
| Male-to-Female ratio | 1.6 : 1 | 1.5 : 1 | 1 : 3.2 |
| Pathophysiology | Progressive degeneration of anterior horn cells and upper and lower motor neurons | Loss of dopaminergic neurons in substantia nigra | Idiopathic inflammation of the central nervous system characterized by demyelinization and axonal degeneration |
| Mean age at diagnosis | 47–52 (familial) 58–63 (sporadic) | 60–70 | 18–35 |
| Diagnostic tests | Clinical diagnosis and electromyography | Clinical diagnosis | Clinical diagnosis, supplemented by magnetic resonance imaging of brain and spinal cord; sensory evoked potential testing; and cerebrospinal fluid analysis |
| Mean survival from time of diagnosis | 3–5 years | Normal life expectancy | Life expectancy 6–7 years less than normal |
| Disease-modifying agents | Riluzole (prolongs survival by 3 months) | None | Beta-interferons Mitoxantrone Glatiramer acetate |
| Signs/symptoms at presentation | Weakness | Bradykinesia | Optic neuritis |
| Spasticity | Rigidity | Paresthesias | |
| Cramps | Rest tremor | Limb weakness | |
| Fasciculations | Postural instability | Impaired coordination | |
| Signs/symptoms in advanced disease | Dysphagia Respiratory failure Sialorrhea Pain | Dysphagia Levodopa induced movement disorders Sialorrhea | Spasticity Pain Bowel/bladder dysfunction Fatigue Depression |
| Clinical course | Progressive | Progressive | Relapsing-remitting Primary progressive Secondary progressive |
Common Elements of Care
Despite wide variation in the clinical manifestations of ND, certain key elements are common to most ND patients and should be integrated as part of standardized care.
Advance Directives/Goals of Care
Patients in general have difficulty initiating discussions regarding goals for their care. Despite a general awareness of the incurable nature of ND, it remains particularly uncommon for these patients to identify a substitute decision maker or have in place a formal advance directive. It is therefore incumbent upon interprofessional teams to provide guidance regarding advance directive completion and ensure that discussions addressing patient goals are a part of routine clinical assessment. The goals of an individual patient may change over time, highlighting the critical importance of consistent revisiting and ongoing documentation.
Key Decisions
Given the progressive nature of ND and the eventual likelihood of both dysphagia and respiratory insufficiency, patients commonly face key decisions relating to corresponding clinical interventions. Patients and families often carry strong beliefs and values related to these decisions, and the interprofessional team must ensure timely, consistent, and effective communication and education. Team members should remain aware that cognitive impairment is a common feature of ND that must influence the timing of all discussions concerning key decisions and goals of care. In subsequent sections addressing management of specific symptoms, current evidence regarding impact on quality of life and survival for nutritional and respiratory interventions will be outlined.
Nutritional Support
The presence of key clinical features determines the level of urgency for discussions related to the insertion and use of a percutaneous gastrostomy tube (PGT). Potential indications include acceleration of weight loss, frequent choking, and/or impaired quality of life because of stress surrounding eating. The aim of PGT use should not be to prevent aspiration, as PGT use is itself associated with this risk. Overall safety of PGT insertion can be gauged by respiratory function, and in particular by forced vital capacity (FVC), because procedural risks increase when FVC is less than 50% of the predicted value.
Respiratory Support
Symptoms suggestive of respiratory insufficiency include breathlessness, sleep disturbances, appetite loss, excessive fatigue, and daytime sleepiness. Despite limited sensitivity, FVC is widely used to assess respiratory insufficiency because symptoms often correlate with values less than 50% of the predicted value. Both nocturnal oximetry and sniff nasal inspiratory nasal pressure (SNIP) are more sensitive tools to evaluate respiratory insufficiency. However, any symptom or sign of respiratory insufficiency should prompt discussions with patients and their caregivers regarding the potential use of noninvasive positive pressure ventilation (NIPPV) and mechanical ventilation (MV).
Clinicians are strongly encouraged to initiate discussions addressing these key decisions early in the course of illness. Even in the absence of symptoms, early discussion and decision making is, in general, welcomed by patients and families and not associated with a loss of hope or distress.
Interprofessional Care and Collaboration
Given the complex needs of ND patients and their families, it has been proposed that dedicated interprofessional teams may be better suited to ensure that care is comprehensive and coordinated. In addition, improvements in both quality of life and survival have been demonstrated in the setting of care delivered by an interprofessional team.
Role of Palliative Care
Although involvement of palliative care has been associated with improvements in overall quality of life for patients with ND, it remains unclear which specific elements of care should routinely be provided by clinicians with palliative care expertise. To provide comprehensive care to patients with ND and their families, it is necessary to identify the primary palliative care competencies required of individual interprofessional team members. Secondary and tertiary palliative care expertise should be accessed if the clinical and symptom needs of patients are complex and unresponsive to primary level interventions.
With the intent of addressing myths regarding palliative care, interprofessional team members, including neurology clinicians not from the palliative care team, should be encouraged to label symptomatic interventions as “palliative in nature”—that is, not intended to modify disease. If consistent, these efforts support an increased understanding that palliative care occurs throughout the ND trajectory and is not “saved” for end of life.
The following are suggested specific roles for palliative care (possibly palliative care specialists, depending on the setting) in the care of ND patients and families:
- 1
Direct care. Palliative care clinicians can address the complex physical and psychosocial symptom issues of ND patients and provide end-of-life care.
- 2
Patient/team experience. Early identification to the patient of palliative care expertise as an integral component of the team enables education of patients and families regarding the possible current and future role for specialist palliative care clinicians.
- 3
Advocacy. Advocacy may include participation and/or facilitation of institutional policy development addressing advanced care planning, national policy development regarding long-term mechanical ventilation, or laws related to physician-assisted suicide.
Given the trajectory and often complex symptom burden ALS patients experience, many advocate for the involvement of palliative care expertise soon after diagnosis. In contrast, PD and MS continue to be considered more chronic in nature, resulting in a less clarity regarding appropriate integration of palliative care expertise.
Symptom Management
The disease-related symptom burden impacting the daily experience of ND patients may lead to substantial distress and, for many, an unacceptable quality of life. Efforts to support a greater emphasis on patient-centered care have led many institutions to integrate the routine use of valid and reliable symptom severity screening tools. Tools targeted for ND patients can serve as a starting point for further dialogue, have the potential to identify physical and psychosocial symptoms before reaching a severe or crisis level, and support the development of targeted symptom management strategies.
Sialorrhea
Sialorrhea (drooling) may feature prominently in ND, with reported rates of 50% and 70% to 80% in patients with ALS and PD, respectively. Sialorrhea typically develops secondary to dysphagia or weakness of orofacial muscles, such that the normal volume of daily saliva production (1.5 L/day) manifests as drooling. Sialorrhea negatively impacts quality of life both physically (e.g., irritation of perioral skin, worsening dysarthria) and psychosocially (e.g., embarrassment, isolation). Treatment strategies are directed at decreasing the volume of saliva produced and summarized in Table 30-2 . Anticholinergics are the most common class of medication used in the management of ND-related sialorrhea. Despite efficacy, significant adverse effects (e.g., delirium) may limit the use of these medications for ND patients with cognitive impairment.
| Treatment | Comments |
|---|---|
| Nonpharmacologic | |
| Manual suction | May cause agitation in end-stage disease |
| Chest physiotherapy with postural drainage | |
| Incentive spirometry | |
| High-frequency chest wall oscillation | Effective in cystic fibrosis; no evidence specific to ALS |
| Mechanical insufflation/exsufflation | Recommended by ALS practice parameter (6) |
| Pharmacologic | |
| Glycopyrrolate (0.5 mg PO bid or tid) | |
| Scopolamine (1 patch every 3 days) | |
| Amitriptyline (10–150 mg qd) | Also indicated to treat pseudobulbar affect and depression |
| Atropine 1% eye drops (1–3 drops q4h) | |
| Interventions | |
| Botulinum toxin (10,11) | Maximum response at 4 weeks; duration of action up to 4 months; may cause transient dysphagia |
| Radiation to parotid and/or submandibular glands (10) | Duration of action up to 6 months; may cause xerostomia |
Spasticity and Cramps
Spasticity, or increased muscle tone, is a manifestation of upper motor neuron dysfunction and is a symptom commonly encountered in both ALS and MS. Patients typically complain of stiffness, immobility, involuntary spasms, joint contractures, and pain.
Occupational therapy and physiotherapy team members play a critical role in the management of spasticity through individualizing appropriate stretching and range-of-motion exercises, splints, and orthotics. Aggressive treatment of spasticity is critically important because the level of severity for any given patient directly correlates with an ability to both transfer and ambulate. Although uncommon, refractory spasticity may be treated with a continuous intrathecal baclofen infusion. Efficacy has been demonstrated in a small cohort of ALS patients with no reported neurologic morbidity or mortality. Therapeutic interventions for spasticity are summarized in Table 30-3 .
| Treatment | Comments |
|---|---|
| Nonpharmacologic | |
| Moderate exercise | |
| Pharmacologic | |
| Baclofen (10–40 mg tid) | Can cause weakness and fatigue |
| Tizanidine (2–8 mg tid) | Can cause weakness and fatigue |
| Dantrolene (50–100 mg qid) | |
| Clonazepam (0.5–1.0 mg tid) | |
| Gabapentin (300–900 mg tid) | Can cause weakness and fatigue |
| Cannabinoids (THC) (5–10 mg/day) | |
| Interventions | |
| Botulinum toxin (14) | Specific to MS |
| Intrathecal baclofen (13) | For intractable spasticity |
Muscle cramps are a manifestation of lower motor neuron dysfunction and are commonly encountered in patients with ALS. Relief may be obtained with physical therapy (e.g., passive stretching and massage) or quinine (400 mg/day).
Motor Complications in Parkinson’s Disease
Motor complications in PD comprise a group of aberrant movement phenomena that typically emerge after 5 to 7 years of levodopa therapy. Long-term levodopa therapy can result in drug-induced dyskinesias (involuntary choreiform movements involving the head, trunk, and limbs), dystonias (sustained or repetitive involuntary muscle contractions), and motor fluctuations. Specific motor symptoms include the following:
- •
“Wearing-off”: Increasingly shorter duration of therapeutic benefit following each dose of levodopa; associated with reemergence of Parkinsonian symptoms
- •
“On-off” fluctuations: Unpredictable and abrupt fluctuations in motor state from times of symptom control (“on”) to times of worsening Parkinsonian symptoms (“off”)
- •
Hypokinesis/akinesis: Near immobility associated with “off” periods of dopaminergic treatment
- •
Dyskinesias/dystonias: Abnormal involuntary movements that may be choreic (typical during “on” periods) or dystonic (can occur during either “on” or “off” periods)
- •
“Freezing”: Near akinesis when initiating walking, turning, or ambulating past visual barriers
The general management of motor symptoms in advanced PND involves levodopa dose adjustments and initiation of adjuvant medications. Specific strategies include the following:
- •
Fractionate levodopa dosing (lower, more frequent doses)
- •
Addition of a dopamine agonist (e.g., bromocriptine, pergolide, pramipexole, ropinirole)
- •
Addition of a catechol-O-methyltransferase (COMT) inhibitor (e.g., entacapone, tolcapone)
- •
Addition of a monoamine oxidase-B inhibitor (e.g., selegiline, rasagiline)
- •
Addition of amantadine
“Freezing” is poorly responsive to increases in dopaminergic medication but may respond to sensory stimulation and assisted devices. For advanced motor symptoms poorly responsive to conventional management techniques, parenteral apomorphine (a powerful dopamine agonist) is indicated. In addition, surgical interventions such as deep brain stimulation of the subthalamic nucleus and unilateral pallidotomy can be effective in treating refractory motor complications.
Nonmotor Complications in Parkinson’s Disease
Unlike motor complications, symptoms associated with nonmotor complications in PD do not respond to adjustments in dopaminergic therapy.
Autonomic Dysfunction
Common symptoms of autonomic dysfunction include urinary dysfunction and orthostatic hypotension. Symptoms such as urinary frequency and urgency, nocturia, and urge incontinence may be treated with oxybutynin (5 mg two or three times daily) and/or tolterodine (1–2 mg twice daily). These agents have not been specifically studied in PD, however, and may worsen cognitive symptoms.
Postural Hypotension
Management strategies include reassessment of antihypertensive medications, if applicable, and the addition of agents such as midodrine (2.5 mg two to three times daily) and/or fludrocortisone (0.1 mg two or three times daily).
Pain
In the setting of nonmalignant disease, pain is in general poorly assessed and undertreated. Additionally, the evidence base from which to guide treatment decisions is sparse. A recent Cochrane review examining the medical management of pain in ALS failed to identify any randomized controlled trials or quasi-randomized trials.
Physical weakness, debilitation, and impaired mobility serve as potential sources for pain in the setting of ND. Patients affected by upper motor neuron (UMN) dysfunction resulting in spasticity or lower motor neuron dysfunction (LMN) resulting in weakness present with symptoms of musculoskeletal pain such as stiffness and contractures. General principles for the assessment and treatment of pain should be applied. The expert recommendations of occupational therapy and physiotherapy professionals are essential components of a comprehensive management plan. Pharmacologic management typically begins with agents such as acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), and muscle relaxants. If adequate relief is not achieved with nonpharmacologic techniques in combination with nonopioid analgesics, the introduction of opioids should be considered in accordance with the World Health Organization (WHO) guidelines.
Unlike ALS and PD, pain is a well-described clinical entity for patients with MS. Estimates of pain prevalence in MS range from 29% to 86%, with both neuropathic and nociceptive-somatic pain syndromes having been described. Examples of nociceptive pain include painful tonic spasms, musculoskeletal back pain, and headache. The most common types of neuropathic pain include dysthetic extremity pain, trigeminal neuralgia, and Lhermitte’s sign (a transient sensation related to neck movement). Although no efficacy trials have compared various analgesics, options include anti-epileptics (gabapentin and pregabalin), NSAIDS, opioids, tricyclic antidepressants (TCAs), and antispasmodic agents (see Spasticity and Cramps ). In a recent consensus guideline, cannabinoids were positioned as second-line agents, given the lack of randomized controlled trials and concerns regarding long-term safety. In the setting of refractory pain, interventional pain management strategies such as nerve blocks have also been reported to be effective.
Breathlessness
Progressive respiratory muscle weakness in patients with ND may eventually result in the sensation of breathlessness. This can occur with exertion or at rest and can initially present with a history suggestive of nocturnal hypoventilation—that is, disordered sleep and daytime fatigue.
Although routine clinical screening and assessment of breathlessness (including both history and investigations) can support decision making regarding future interventions, management of the symptom itself should not be delayed. Specific strategies are outlined in Table 30-4 .
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
